Susceptibility in vitro of canine methicillin-resistant and -susceptible staphylococcal isolates to fusidic acid, chlorhexidine and miconazole: opportunities for topical therapy of canine superficial pyoderma

OBJECTIVES: Increasing multidrug resistance amongst canine pathogenic staphylococci has renewed interest in topical antibacterial therapy for skin infections in the context of responsible veterinary prescribing. We therefore determined the activity in vitro of three clinically relevant topical agents and synergism between two of them against Staphylococcus pseudintermedius and Staphylococcus aureus. METHODS: The MICs of fusidic acid (n = 199), chlorhexidine (n = 198), miconazole (n = 198) and a 1:1 combination of miconazole/chlorhexidine (n = 198) were determined for canine isolates [50 MRSA and 49 methicillin-resistant S. pseudintermedius (MRSP), 50 MSSA and 50 methicillin-susceptible S. pseudintermedius (MSSP)] collected from the UK and Germany using an agar dilution method (CLSI VET01-A4). Fractional inhibitory concentration (FIC) indices were calculated to assess the interaction of miconazole with chlorhexidine. RESULTS: MICs of each drug/combination were significantly (P < 0.0005) higher for S. aureus when compared with S. pseudintermedius. Most strains (n = 172) had an MIC of fusidic acid of ≤0.03 mg/L (MIC ≥64 mg/L, n = 5 MRSA). All strains had MICs of chlorhexidine of 0.5–4 mg/L, except for one MRSA (MIC = 8 mg/L). All but four strains had MICs of miconazole of 1–4 mg/L (MIC = 16 mg/L, n = 3; MIC = 256 mg/L, n = 1). Miconazole/chlorhexidine (1:1 ratio) had a synergistic effect against 49/50 MRSA, 31/50 MSSA, 12/49 MRSP and 23/49 MSSP. CONCLUSIONS: Since the majority of these staphylococci, including methicillin-resistant isolates, had MICs that should be readily exceeded by topical skin application of these agents, their therapeutic efficacy for canine superficial pyoderma should be assessed. The synergistic interaction shown in vitro supports further clinical evaluation of miconazole/chlorhexidine combination therapy for staphylococcal infection

TARGET2 Unlimited: Monetary Policy Implications of Asymmetric Liquidity Management within the Euro Area

This paper analyses the implications of a continued divergence of TARGET2 balances for monetary policy in the euro area. The accumulation of TARGET2 claims (liabilities) would make ECB’s liquidity management asymmetric once the TARGET2 claims in core countries have crowded out central bank credit in those regions. Then while providing scarce liquidity to banks in countries with TARGET2 liabilities, the ECB will need to absorb excess liquidity in countries with TARGET2 claims. We discuss three alternatives and its implications to absorb excess liquidity in core regions: (1) Using market based measures might accelerate the capital flight from periphery to core countries and would add to the accumulation of risky assets by the ECB. (2) Conducting non-market based measures such as imposing differential (unremunerated) reserve requirements would distort banking markets and would support the development of shadow banking. (3) Staying passive would lead to decreasing interest rates in core Europe entailing inflationary pressure and overinvestment in those regions and possibly future instability of the banking system.TARGET2 balances, monetary policy, euro area, Eurosystem, excess liquidity

The effect of new oral anticoagulants and extended thromboprophylaxis policy on hip and knee arthroplasty outcomes: observational study

The efficacy and safety of the new oral anticoagulants (NOAC) and the benefits of extended duration thromboprophylaxis following hip and knee replacements remain uncertain. This observational study describes the relations between thromboprophylaxis policies following hip and knee replacements across England's NHS and patient outcomes between January 2008 and December 2011. From the national administrative database, we analyzed mortality, thromboembolic complications, emergency readmission, and bleeding rates for 201,418 hip and 230,282 knee replacements. There were no differences in outcomes for either LMWH or NOAC. We found no advantage in favor of any single anticoagulation policy or in changing policy. This study supports the American Academy of Orthopaedic Surgeons' recommendation that the choice and duration of thromboprophylaxis prophylaxis be decided by the treating surgeon

The Golden Fountain - Is urine the miracle drug no one told you about?

The supposed indications for urine therapy, ancient or contemporary, are too numerous to recite. There is, it seems, virtually nothing urine won’t cure. Modern proponents use pseudoscience to explain the benefits of the various, mostly exaggerated, components of urine. Some hint at a conspiracy by the medical establishment and the pharmaceutical industry to keep the knowledge of the many fantastic healing properties of cheaply available urine a secret. There is no money to be made from urine, well, unless one was to write a book about its many virtues. But, seriously, what do we really know

Closed-loop recycling of plastics enabled by dynamic covalent diketoenamine bonds.

Recycled plastics are low-value commodities due to residual impurities and the degradation of polymer properties with each cycle of re-use. Plastics that undergo reversible polymerization allow high-value monomers to be recovered and re-manufactured into pristine materials, which should incentivize recycling in closed-loop life cycles. However, monomer recovery is often costly, incompatible with complex mixtures and energy-intensive. Here, we show that next-generation plastics-polymerized using dynamic covalent diketoenamine bonds-allow the recovery of monomers from common additives, even in mixed waste streams. Poly(diketoenamine)s 'click' together from a wide variety of triketones and aromatic or aliphatic amines, yielding only water as a by-product. Recovered monomers can be re-manufactured into the same polymer formulation, without loss of performance, as well as other polymer formulations with differentiated properties. The ease with which poly(diketoenamine)s can be manufactured, used, recycled and re-used-without losing value-points to new directions in designing sustainable polymers with minimal environmental impact

Let’s do the time warp again – embodied learning of the concept of time in an applied school setting

This article has been accepted for publication in Interactive Learning Environments, published by Taylor & Francis. Embodied Cognition approaches suggest that movements influence the understanding of abstract concepts such as time. It follows that moving the arms as watch hands should boost children’s learning to read the clock. In a school setting, we compared three learning conditions: an embodied (movement) condition, an interactive App condition, and a text condition. Age, self-reported enjoyment, and group size were controlled. In a clock-time-test, the embodied condition resulted in better performances than the mean of the other conditions in small, but not in large groups. This innovative, theory-informed approach may advance learning of abstract concepts in children

Genomic insights into the rapid emergence and evolution of MDR in Staphylococcus pseudintermedius.

OBJECTIVES: MDR methicillin-resistant Staphylococcus pseudintermedius (MRSP) strains have emerged rapidly as major canine pathogens and present serious treatment issues and concerns to public health due to their, albeit low, zoonotic potential. A further understanding of the genetics of resistance arising from a broadly susceptible background of S. pseudintermedius is needed. METHODS: We sequenced the genomes of 12 S. pseudintermedius isolates of varied STs and resistance phenotypes. RESULTS: Nine distinct clonal lineages had acquired either staphylococcal cassette chromosome (SCC) mec elements and/or Tn5405-like elements carrying up to five resistance genes [aphA3, sat, aadE, erm(B), dfrG] to generate MRSP, MDR methicillin-susceptible S. pseudintermedius and MDR MRSP populations. The most successful and clinically problematic MDR MRSP clones, ST68 SCCmecV(T) and ST71 SCCmecII-III, have further accumulated mutations in gyrA and grlA conferring resistance to fluoroquinolones. The carriage of additional mobile genetic elements (MGEs) was highly variable, suggesting that horizontal gene transfer is frequent in S. pseudintermedius populations. CONCLUSIONS: Importantly, the data suggest that MDR MRSP evolved rapidly by the acquisition of a very limited number of MGEs and mutations, and that the use of many classes of antimicrobials may co-select for the spread and emergence of MDR and XDR strains. Antimicrobial stewardship will need to be comprehensive, encompassing human medicine and veterinary disciplines to successfully preserve antimicrobial efficacy